Sphingomyelin synthases 1 and 2 exhibit phosphatidylcholine phospholipase C activity |
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Authors: | Yeun-po Chiang Zhiqiang Li Yang Chen Yu Cao Xian-Cheng Jiang |
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Affiliation: | 1.Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA;2.Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, Brooklyn, New York, USA;3.Institute of Precision Medicine, Ninth People''s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China |
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Abstract: | Many studies have confirmed the enzymatic activity of a mammalian phosphatidylcholine (PC) phospholipase C (PLC) (PC-PLC), which produces diacylglycerol (DAG) and phosphocholine through the hydrolysis of PC in the absence of ceramide. However, the protein(s) responsible for this activity have never yet been identified. Based on the fact that tricyclodecan-9-yl-potassium xanthate can inhibit both PC-PLC and sphingomyelin synthase (SMS) activities, and SMS1 and SMS2 have a conserved catalytic domain that could mediate a nucleophilic attack on the phosphodiester bond of PC, we hypothesized that both SMS1 and SMS2 might have PC-PLC activity. In the present study, we found that purified recombinant SMS1 and SMS2 but not SMS-related protein have PC-PLC activity. Moreover, we prepared liver-specific Sms1/global Sms2 double-KO mice. We found that liver PC-PLC activity was significantly reduced and steady-state levels of PC and DAG in the liver were regulated by the deficiency, in comparison with control mice. Using adenovirus, we expressed Sms1 and Sms2 genes in the liver of the double-KO mice, respectively, and found that expressed SMS1 and SMS2 can hydrolyze PC to produce DAG and phosphocholine. Thus, SMS1 and SMS2 exhibit PC-PLC activity in vitro and in vivo. |
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Keywords: | phosphatidylcholine phospholipase C (PC-PLC) sphingomyelin synthase 1 and 2 phosphatidylcholine diacylglycerol sphingomyelin |
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